Osteoporosis ranks as a major public health problem in the United States. Estimates are that by the year 2050, the incidence of this disabling disorder will significantly increase both in terms of the numbers of women and men affected, and an escalating cost of patient care. Several studies indicate that genetic factors play a major role in the development of osteoporosis both in terms of peak young adult bone mass and perhaps in the rates of bone loss with age. The data also suggests that osteoporosis is a complex disorder, and that several genes interact to set the stage for bone loss with advancing age and in certain younger individuals. The Old Order Amish of Lancaster County, Pennsylvania, are a homogeneous population that is ideal for the identification of osteoporosis susceptibility genes by positional cloning methodology. Probands will be ascertained based on the occurrence of vertebral or hip fracture. Males with idiopathic primary osteoporosis are also a target population for the identification of these genes. Phenotype analysis will include measurements of bone mineral density, family history, dietary analysis, and history of exposure to estrogen and testosterone. Genome-wide scans for osteoporosis susceptibility genes will be accomplished by Gene/Networks, Allemeda, CA, using high throughput automated methods to construct a 10 centimorgan map. Identification of osteoporosis susceptibility genes would be crucial in planning strategies for identification of persons at risk, and for developing effective therapeutic interventions.